Turcot syndrome

Turcot syndrome is a hereditary cancer predisposition syndrome that links colorectal polyposis with malignant brain tumors, representing an overlap between two major polyposis/cancer syndromes: Familial Adenomatous Polyposis (FAP) and Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer, HNPCC). There are two molecular subtypes: Type 1 involves mutations in DNA mismatch repair genes (MLH1, PMS2), leading to microsatellite instability, multiple colonic adenomas (fewer than classic FAP), and association with glioblastoma multiforme. Type 2 involves APC gene mutations (same gene as FAP, located on chromosome 5q21), leading to numerous colonic adenomatous polyps and association with medulloblastoma. Clinically, patients present in childhood or young adulthood with neurological symptoms from the brain tumor (headache, ataxia, seizures, focal deficits) and/or gastrointestinal symptoms from colonic polyposis (rectal bleeding, anemia, change in bowel habits). Diagnosis involves colonoscopy revealing polyposis, brain imaging (MRI) for tumor detection, and genetic testing to identify APC or mismatch repair gene mutations. Skin findings such as café-au-lait spots may also be present. Management requires a multidisciplinary approach: surgical resection of the CNS tumor with adjuvant chemotherapy/radiation as indicated, and prophylactic colectomy for polyposis to prevent colorectal cancer, along with genetic counseling for at-risk family members. This syndrome is high-yield for USMLE because it tests knowledge of the APC gene pathway (Wnt/β-catenin signaling) and mismatch repair mechanisms, linking colorectal cancer syndromes to CNS tumor pathology—an important integration of GI, oncology, and neuropathology concepts. It is often compared with Gardner syndrome (FAP + osteomas/soft tissue tumors) and Lynch syndrome (HNPCC) in board exam vignettes.